Cellular Transplantation Biology, Division of Cancer Medicine, Kanazawa University Graduate School of Medical Science, Ishikawa, Japan.
Br J Haematol. 2009 Oct;147(1):102-12. doi: 10.1111/j.1365-2141.2009.07822.x. Epub 2009 Jul 28.
Peripheral blood from 489 recently diagnosed patients with aplastic anaemia (AA) and 316 with refractory anaemia (RA) of myelodysplastic syndrome was evaluated to characterize CD55(-)CD59(-) [paroxysmal nocturnal haemoglobinuria (PNH)]-type blood cells associated with bone marrow (BM) failure. PNH-type cells were detected in 57% and 20% of patients with AA and RA, respectively. The percentages of PNH-type granulocytes ranged from 0.003% to 94.2% and the distribution was log-normal with a median of 0.178%. Serial analyses of 75 patients with PNH-type cells over 5 years revealed that the percentage of PNH-type cells constantly increased in 13 (17%), persisted in 44 (59%), disappeared in the remaining 18 (24%) although even in the 'Disappearance' group, PNH-type granulocytes persisted for at least 6 months. A scattergram profile of PNH-type cells unique to each patient persisted regardless of the response to immunosuppressive therapy and only single PIGA mutations were detected in PNH-type granulocytes sorted from four patients. These findings suggest that the PNH-type cells in patients with BM failure are derived from single PIGA mutant haematopoietic stem cells even when their percentages are <1% and their fate depends on the proliferation and self-maintenance properties of the individual PIGA mutants.
对 489 例新诊断的再生障碍性贫血（AA）患者和 316 例骨髓增生异常综合征难治性贫血（RA）患者的外周血进行了评估，以确定与骨髓衰竭相关的 CD55(-)CD59(-) [阵发性夜间血红蛋白尿症（PNH）] 型血细胞。在 AA 和 RA 患者中，分别有 57%和 20%的患者检测到 PNH 型细胞。PNH 型粒细胞的百分比范围为 0.003%至 94.2%，分布呈对数正态分布，中位数为 0.178%。对 75 例 PNH 型细胞患者进行了 5 年的连续分析，结果表明，在 13 例（17%）患者中，PNH 型细胞的百分比持续增加，在 44 例（59%）患者中持续存在，在其余 18 例（24%）患者中消失，尽管在“消失”组中，PNH 型粒细胞至少持续存在 6 个月。每个患者的 PNH 型细胞散点图特征无论对免疫抑制治疗的反应如何都保持不变，仅在从 4 例患者中分选的 PNH 型粒细胞中检测到单个 PIGA 突变。这些发现表明，骨髓衰竭患者的 PNH 型细胞源自单个 PIGA 突变造血干细胞，即使其百分比<1%，其命运取决于个体 PIGA 突变体的增殖和自我维持特性。
